Chronic exercise programs have several advantages when compared to caloric restriction for the treatment of obesity. Chronic exercise produces similar losses of fat mass as underfeeding but lean body mass is maintained. The maintenance of muscle mass during weight loss is thought to be beneficial for long-term weight control. Thyroid hormones are important regulators of protein synthesis and catabolism and are themselves regulated by both diet and exercise. It is hypothesized that exercise- induced alterations in thyroid hormone metabolism are responsible, in part, for the effects of exercise on muscle protein metabolism. The goals of this study are to characterize the roles of exercise and thyroid hormones in regulating muscle protein metabolism and determine the molecular mechanisms by which exercise and thyroid hormones modulate these effects. Chronic voluntary exercise in the form of running well activity will be combined with alterations in the levels of thyroid hormones and caloric intake in a rat model to produce both possible and negative caloric balance. The independent effects of exercise and caloric balance on thyroid hormone metabolism will be clarified by measurements of thyroxine (T4) and triiodothyronine (T3) production and conversion of T4 to T3 in vivo. Characterization of the effects of thyroid hormones on muscle protein content, protein synthesis, DNA and RNA content, and mRNA species of specific muscle proteins during exercise will be performed in thyroidectectomized rats replaced with low, normal or increased levels of thyroid hormone. These studies will be performed using both weight matched and pair-fed controls. The studies will afford us an opportunity to study the roles of thyroid hormones and physical activity on the regulation of muscle protein synthesis. The results of these studies should provide important information on the regulation of lean body mass during exercise and caloric restriction. Increasing our knowledge of the interaction of caloric intake, thyroid hormones, and exercise is important in providing the proper exercise treatment program for patients with disease states including diabetes mellitus, obesity and atherosclerotic heart disease. These studies should provide basis for future studies into the molecular biology of the effects of exercise on regulation of thyroid and protein synthesis.